H2AX_MOUSE
ID H2AX_MOUSE Reviewed; 143 AA.
AC P27661;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Histone H2AX;
DE Short=H2a/x;
DE AltName: Full=Histone H2A.X;
GN Name=H2ax {ECO:0000312|MGI:MGI:102688};
GN Synonyms=H2a.x, H2afx {ECO:0000312|MGI:MGI:102688}, Hist5-2ax;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv;
RX PubMed=2041781; DOI=10.1093/nar/19.9.2441;
RA Nagata T., Kato T., Morita T., Nozaki M., Kubota H., Yagi H.,
RA Matsushiro A.;
RT "Polyadenylated and 3' processed mRNAs are transcribed from the mouse
RT histone H2A.X gene.";
RL Nucleic Acids Res. 19:2441-2447(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C3H/HeJ; TISSUE=Placenta;
RX PubMed=7774939; DOI=10.1016/0888-7543(95)80145-c;
RA Porcher C., Grandchamp B.;
RT "Structure of the mouse H2A.X gene and physical linkage to the UPS locus on
RT chromosome 9: assignment of the human H2A.X gene to 11q23 by sequence
RT analysis.";
RL Genomics 25:312-313(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP UBIQUITINATION.
RX PubMed=7407044; DOI=10.1021/bi00555a022;
RA West M.H.P., Bonner W.M.;
RT "Histone 2A, a heteromorphous family of eight protein species.";
RL Biochemistry 19:3238-3245(1980).
RN [5]
RP PHOSPHORYLATION AT SER-2, AND ACETYLATION AT SER-2.
RX PubMed=7217105; DOI=10.1016/s0021-9258(19)69487-1;
RA Pantazis P., Bonner W.M.;
RT "Quantitative determination of histone modification. H2A acetylation and
RT phosphorylation.";
RL J. Biol. Chem. 256:4669-4675(1981).
RN [6]
RP PHOSPHORYLATION AT SER-140.
RX PubMed=9488723; DOI=10.1074/jbc.273.10.5858;
RA Rogakou E.P., Pilch D.R., Orr A.H., Ivanova V.S., Bonner W.M.;
RT "DNA double-stranded breaks induce histone H2AX phosphorylation on serine
RT 139.";
RL J. Biol. Chem. 273:5858-5868(1998).
RN [7]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-140.
RX PubMed=11571274; DOI=10.1074/jbc.c100466200;
RA Burma S., Chen B.P., Murphy M., Kurimasa A., Chen D.J.;
RT "ATM phosphorylates histone H2AX in response to DNA double-strand breaks.";
RL J. Biol. Chem. 276:42462-42467(2001).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-140.
RX PubMed=11740565; DOI=10.1038/414660a;
RA Petersen S., Casellas R., Reina-San-Martin B., Chen H.T.,
RA Difilippantonio M.J., Wilson P.C., Hanitsch L., Celeste A., Muramatsu M.,
RA Pilch D.R., Redon C., Ried T., Bonner W.M., Honjo T., Nussenzweig M.C.,
RA Nussenzweig A.;
RT "AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations
RT at sites of class switching.";
RL Nature 414:660-665(2001).
RN [9]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140, AND TISSUE SPECIFICITY.
RX PubMed=11242108; DOI=10.1038/85830;
RA Mahadevaiah S.K., Turner J.M.A., Baudat F., Rogakou E.P., de Boer P.,
RA Blanco-Rodriguez J., Jasin M., Keeney S., Bonner W.M., Burgoyne P.S.;
RT "Recombinational DNA double-strand breaks in mice precede synapsis.";
RL Nat. Genet. 27:271-276(2001).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-140.
RX PubMed=12447390; DOI=10.1038/ncb884;
RA Fernandez-Capetillo O., Chen H.-T., Celeste A., Ward I., Romanienko P.J.,
RA Morales J.C., Naka K., Xia Z., Camerini-Otero R.D., Motoyama N.,
RA Carpenter P.B., Bonner W.M., Chen J., Nussenzweig A.;
RT "DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1.";
RL Nat. Cell Biol. 4:993-997(2002).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12034884; DOI=10.1073/pnas.122228699;
RA Bassing C.H., Chua K.F., Sekiguchi J., Suh H., Whitlow S.R., Fleming J.C.,
RA Monroe B.C., Ciccone D.N., Yan C., Vlasakova K., Livingston D.M.,
RA Ferguson D.O., Scully R., Alt F.W.;
RT "Increased ionizing radiation sensitivity and genomic instability in the
RT absence of histone H2AX.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:8173-8178(2002).
RN [12]
RP FUNCTION.
RX PubMed=11934988; DOI=10.1126/science.1069398;
RA Celeste A., Petersen S., Romanienko P.J., Fernandez-Capetillo O.,
RA Chen H.T., Sedelnikova O.A., Reina-San-Martin B., Coppola V., Meffre E.,
RA Difilippantonio M.J., Redon C., Pilch D.R., Olaru A., Eckhaus M.,
RA Camerini-Otero R.D., Tessarollo L., Livak F., Manova K., Bonner W.M.,
RA Nussenzweig M.C., Nussenzweig A.;
RT "Genomic instability in mice lacking histone H2AX.";
RL Science 296:922-927(2002).
RN [13]
RP FUNCTION.
RX PubMed=12914700; DOI=10.1016/s0092-8674(03)00566-x;
RA Bassing C.H., Suh H., Ferguson D.O., Chua K.F., Manis J., Eckersdorff M.,
RA Gleason M., Bronson R., Lee C., Alt F.W.;
RT "Histone H2AX: a dosage-dependent suppressor of oncogenic translocations
RT and tumors.";
RL Cell 114:359-370(2003).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF SER-137 AND SER-140.
RX PubMed=12914701; DOI=10.1016/s0092-8674(03)00567-1;
RA Celeste A., Difilippantonio S., Difilippantonio M.J.,
RA Fernandez-Capetillo O., Pilch D.R., Sedelnikova O.A., Eckhaus M., Ried T.,
RA Bonner W.M., Nussenzweig A.;
RT "H2AX haploinsufficiency modifies genomic stability and tumor
RT susceptibility.";
RL Cell 114:371-383(2003).
RN [15]
RP FUNCTION.
RX PubMed=12689589; DOI=10.1016/s1534-5807(03)00093-5;
RA Fernandez-Capetillo O., Mahadevaiah S.K., Celeste A., Romanienko P.J.,
RA Camerini-Otero R.D., Bonner W.M., Manova K., Burgoyne P., Nussenzweig A.;
RT "H2AX is required for chromatin remodeling and inactivation of sex
RT chromosomes in male mouse meiosis.";
RL Dev. Cell 4:497-508(2003).
RN [16]
RP INTERACTION WITH TP53BP1.
RX PubMed=12697768; DOI=10.1074/jbc.c300117200;
RA Ward I.M., Minn K., Jorda K.G., Chen J.;
RT "Accumulation of checkpoint protein 53BP1 at DNA breaks involves its
RT binding to phosphorylated histone H2AX.";
RL J. Biol. Chem. 278:19579-19582(2003).
RN [17]
RP FUNCTION, AND PHOSPHORYLATION AT SER-140.
RX PubMed=12660252; DOI=10.1074/jbc.m300198200;
RA Furuta T., Takemura H., Liao Z.-Y., Aune G.J., Redon C., Sedelnikova O.A.,
RA Pilch D.R., Rogakou E.P., Celeste A., Chen H.T., Nussenzweig A.,
RA Aladjem M.I., Bonner W.M., Pommier Y.;
RT "Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1
RT in response to replication-dependent DNA double-strand breaks induced by
RT mammalian DNA topoisomerase I cleavage complexes.";
RL J. Biol. Chem. 278:20303-20312(2003).
RN [18]
RP FUNCTION, AND PHOSPHORYLATION AT SER-140.
RX PubMed=14530383; DOI=10.1083/jcb.200305124;
RA Fernandez-Capetillo O., Liebe B., Scherthan H., Nussenzweig A.;
RT "H2AX regulates meiotic telomere clustering.";
RL J. Cell Biol. 163:15-20(2003).
RN [19]
RP FUNCTION.
RX PubMed=12792649; DOI=10.1038/ncb1004;
RA Celeste A., Fernandez-Capetillo O., Kruhlak M.J., Pilch D.R., Staudt D.W.,
RA Lee A., Bonner R.F., Bonner W.M., Nussenzweig A.;
RT "Histone H2AX phosphorylation is dispensable for the initial recognition of
RT DNA breaks.";
RL Nat. Cell Biol. 5:675-679(2003).
RN [20]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-140.
RX PubMed=15059890; DOI=10.1158/0008-5472.can-03-3207;
RA Stiff T., O'Driscoll M., Rief N., Iwabuchi K., Loebrich M., Jeggo P.A.;
RT "ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure
RT to ionizing radiation.";
RL Cancer Res. 64:2390-2396(2004).
RN [21]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15589157; DOI=10.1016/j.cub.2004.11.032;
RA Turner J.M.A., Aprelikova O., Xu X., Wang R., Kim S., Chandramouli G.V.R.,
RA Barrett J.C., Burgoyne P.S., Deng C.-X.;
RT "BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome
RT inactivation.";
RL Curr. Biol. 14:2135-2142(2004).
RN [22]
RP FUNCTION.
RX PubMed=15574327; DOI=10.1016/j.molcel.2004.10.029;
RA Riballo E., Kuehne M., Rief N., Doherty A., Smith G.C.M., Recio M.-J.,
RA Reis C., Dahm K., Fricke A., Krempler A., Parker A.R., Jackson S.P.,
RA Gennery A., Jeggo P.A., Loebrich M.;
RT "A pathway of double-strand break rejoining dependent upon ATM, Artemis,
RT and proteins locating to gamma-H2AX foci.";
RL Mol. Cell 16:715-724(2004).
RN [23]
RP FUNCTION, AND MUTAGENESIS OF SER-140.
RX PubMed=15610743; DOI=10.1016/j.molcel.2004.12.007;
RA Xie A., Puget N., Shim I., Odate S., Jarzyna I., Bassing C.H., Alt F.W.,
RA Scully R.;
RT "Control of sister chromatid recombination by histone H2AX.";
RL Mol. Cell 16:1017-1025(2004).
RN [24]
RP FUNCTION.
RX PubMed=15632067; DOI=10.1128/mcb.25.2.661-670.2005;
RA Kang J., Ferguson D., Song H., Bassing C., Eckersdorff M., Alt F.W., Xu Y.;
RT "Functional interaction of H2AX, NBS1, and p53 in ATM-dependent DNA damage
RT responses and tumor suppression.";
RL Mol. Cell. Biol. 25:661-670(2005).
RN [25]
RP FUNCTION, AND PHOSPHORYLATION AT SER-140.
RX PubMed=15580272; DOI=10.1038/ng1484;
RA Turner J.M.A., Mahadevaiah S.K., Fernandez-Capetillo O., Nussenzweig A.,
RA Xu X., Deng C.-X., Burgoyne P.S.;
RT "Silencing of unsynapsed meiotic chromosomes in the mouse.";
RL Nat. Genet. 37:41-47(2005).
RN [26]
RP PHOSPHORYLATION AT TYR-143.
RX PubMed=19092802; DOI=10.1038/nature07668;
RA Xiao A., Li H., Shechter D., Ahn S.H., Fabrizio L.A., Erdjument-Bromage H.,
RA Ishibe-Murakami S., Wang B., Tempst P., Hofmann K., Patel D.J.,
RA Elledge S.J., Allis C.D.;
RT "WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase
RT activity.";
RL Nature 457:57-62(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121; SER-122; SER-137 AND
RP SER-140, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [28]
RP ACETYLATION AT LYS-37, AND MUTAGENESIS OF LYS-6; LYS-10; LYS-14; LYS-16;
RP LYS-37; 119-LYS-LYS-120 AND SER-140.
RX PubMed=20488183; DOI=10.1016/j.febslet.2010.05.017;
RA Jiang X., Xu Y., Price B.D.;
RT "Acetylation of H2AX on lysine 36 plays a key role in the DNA double-strand
RT break repair pathway.";
RL FEBS Lett. 584:2926-2930(2010).
RN [29]
RP SUBCELLULAR LOCATION.
RX PubMed=23039116; DOI=10.1111/gtc.12005;
RA Kogo H., Tsutsumi M., Inagaki H., Ohye T., Kiyonari H., Kurahashi H.;
RT "HORMAD2 is essential for synapsis surveillance during meiotic prophase via
RT the recruitment of ATR activity.";
RL Genes Cells 17:897-912(2012).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6 AND LYS-10, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [31]
RP SUBCELLULAR LOCATION.
RX PubMed=30272023; DOI=10.1038/s42003-018-0154-z;
RA Zhang Q., Shao J., Fan H.Y., Yu C.;
RT "Evolutionarily-conserved MZIP2 is essential for crossover formation in
RT mammalian meiosis.";
RL Commun. Biol. 1:147-147(2018).
RN [32]
RP SUBCELLULAR LOCATION.
RX PubMed=30949703; DOI=10.1093/nar/gkz226;
RA Liu H., Huang T., Li M., Li M., Zhang C., Jiang J., Yu X., Yin Y.,
RA Zhang F., Lu G., Luo M.C., Zhang L.R., Li J., Liu K., Chen Z.J.;
RT "SCRE serves as a unique synaptonemal complex fastener and is essential for
RT progression of meiosis prophase I in mice.";
RL Nucleic Acids Res. 47:5670-5683(2019).
RN [33]
RP SUBCELLULAR LOCATION.
RX PubMed=30746471; DOI=10.1126/sciadv.aau9780;
RA Zhang Q., Ji S.Y., Busayavalasa K., Yu C.;
RT "SPO16 binds SHOC1 to promote homologous recombination and crossing-over in
RT meiotic prophase I.";
RL Sci. Adv. 5:eaau9780-eaau9780(2019).
CC -!- FUNCTION: Variant histone H2A which replaces conventional H2A in a
CC subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin,
CC limiting DNA accessibility to the cellular machineries which require
CC DNA as a template. Histones thereby play a central role in
CC transcription regulation, DNA repair, DNA replication and chromosomal
CC stability. DNA accessibility is regulated via a complex set of post-
CC translational modifications of histones, also called histone code, and
CC nucleosome remodeling. Required for checkpoint-mediated arrest of cell
CC cycle progression in response to low doses of ionizing radiation and
CC for efficient repair of DNA double strand breaks (DSBs) specifically
CC when modified by C-terminal phosphorylation.
CC {ECO:0000269|PubMed:11740565, ECO:0000269|PubMed:11934988,
CC ECO:0000269|PubMed:12034884, ECO:0000269|PubMed:12447390,
CC ECO:0000269|PubMed:12660252, ECO:0000269|PubMed:12689589,
CC ECO:0000269|PubMed:12792649, ECO:0000269|PubMed:12914700,
CC ECO:0000269|PubMed:12914701, ECO:0000269|PubMed:14530383,
CC ECO:0000269|PubMed:15574327, ECO:0000269|PubMed:15580272,
CC ECO:0000269|PubMed:15589157, ECO:0000269|PubMed:15610743,
CC ECO:0000269|PubMed:15632067}.
CC -!- SUBUNIT: The nucleosome is a histone octamer containing two molecules
CC each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and
CC two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of
CC DNA. Interacts with numerous proteins required for DNA damage signaling
CC and repair when phosphorylated on Ser-140. These include MDC1, BRCA1
CC and the MRN complex, composed of MRE11, RAD50, and NBN. Interaction
CC with the MRN complex is mediated at least in part by NBN. Also
CC interacts with DHX9/NDHII when phosphorylated on Ser-140 and MCPH1 when
CC phosphorylated at Ser-140 or Tyr-143. Interacts with ARRB2; the
CC interaction is detected in the nucleus upon OR1D2 stimulation.
CC Interacts with WRAP53/TCAB1 (By similarity). Interacts with TP53BP1
CC (PubMed:12697768). Interacts with HDGFL2 (By similarity).
CC {ECO:0000250|UniProtKB:P16104, ECO:0000269|PubMed:12697768}.
CC -!- INTERACTION:
CC P27661; Q9Z0X1: Aifm1; NbExp=3; IntAct=EBI-495621, EBI-773597;
CC P27661; Q80V62: Fancd2; NbExp=2; IntAct=EBI-495621, EBI-7268304;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11242108,
CC ECO:0000269|PubMed:11571274, ECO:0000269|PubMed:11740565,
CC ECO:0000269|PubMed:12034884, ECO:0000269|PubMed:12447390,
CC ECO:0000269|PubMed:15589157}. Chromosome {ECO:0000269|PubMed:11242108,
CC ECO:0000269|PubMed:11571274, ECO:0000269|PubMed:12034884,
CC ECO:0000269|PubMed:15059890, ECO:0000269|PubMed:15589157,
CC ECO:0000269|PubMed:23039116, ECO:0000269|PubMed:30272023,
CC ECO:0000269|PubMed:30746471, ECO:0000269|PubMed:30949703}.
CC -!- TISSUE SPECIFICITY: Most abundant in testis, thymus and spleen.
CC {ECO:0000269|PubMed:11242108}.
CC -!- DEVELOPMENTAL STAGE: Synthesized in G1 as well as in S-phase.
CC -!- DOMAIN: The [ST]-Q motif constitutes a recognition sequence for kinases
CC from the PI3/PI4-kinase family.
CC -!- PTM: Phosphorylated on Ser-140 (to form gamma-H2AX or H2AX139ph) in
CC response to DNA double strand breaks (DSBs) generated by exogenous
CC genotoxic agents, by stalled replication forks, by meiotic
CC recombination events and during immunoglobulin class switching in
CC lymphocytes. Phosphorylation can extend up to several thousand
CC nucleosomes from the actual site of the DSB and may mark the
CC surrounding chromatin for recruitment of proteins required for DNA
CC damage signaling and repair. Widespread phosphorylation may also serve
CC to amplify the damage signal or aid repair of persistent lesions.
CC Phosphorylation of Ser-140 (H2AX139ph) in response to ionizing
CC radiation is mediated by both ATM and PRKDC while defects in DNA
CC replication induce Ser-140 phosphorylation (H2AX139ph) subsequent to
CC activation of ATR and PRKDC. Dephosphorylation of Ser-140 by PP2A is
CC required for DNA DSB repair. In meiosis, Ser-140 phosphorylation
CC (H2AX139ph) first occurs at synaptonemal complexes during leptotene and
CC is an ATM-dependent response to the formation of programmed DSBs by
CC SPO11. Ser-140 phosphorylation (H2AX139ph) subsequently occurs at
CC unsynapsed regions of both autosomes and the XY bivalent during
CC zygotene and is ATR- and BRCA1-dependent. Ser-140 phosphorylation
CC (H2AX139ph) may also be required for transcriptional repression of
CC unsynapsed chromatin and meiotic sex chromosome inactivation (MSCI),
CC whereby the X and Y chromosomes condense in pachytene to form the
CC heterochromatic XY-body. During immunoglobulin class switch
CC recombination in lymphocytes, Ser-140 phosphorylation (H2AX139ph) at
CC sites of DNA-recombination requires the activation-induced cytidine
CC deaminase AICDA. Phosphorylation at Tyr-143 (H2AXY142ph) by BAZ1B/WSTF
CC determines the relative recruitment of either DNA repair or pro-
CC apoptotic factors. Phosphorylation at Tyr-143 (H2AXY142ph) favors the
CC recruitment of APBB1/FE65 and pro-apoptosis factors such as MAPK8/JNK1,
CC triggering apoptosis. In contrast, dephosphorylation of Tyr-143 by EYA
CC proteins (EYA1, EYA2, EYA3 or EYA4) favors the recruitment of MDC1-
CC containing DNA repair complexes to the tail of phosphorylated Ser-140
CC (H2AX139ph). {ECO:0000269|PubMed:11242108, ECO:0000269|PubMed:11571274,
CC ECO:0000269|PubMed:11740565, ECO:0000269|PubMed:12447390,
CC ECO:0000269|PubMed:12660252, ECO:0000269|PubMed:14530383,
CC ECO:0000269|PubMed:15059890, ECO:0000269|PubMed:15580272,
CC ECO:0000269|PubMed:19092802, ECO:0000269|PubMed:7217105,
CC ECO:0000269|PubMed:9488723}.
CC -!- PTM: Monoubiquitination of Lys-120 (H2AXK119ub) by RING1 and RNF2/RING2
CC complex gives a specific tag for epigenetic transcriptional repression.
CC Following DNA double-strand breaks (DSBs), it is ubiquitinated through
CC 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the
CC E3 ligases RNF8 and RNF168, leading to the recruitment of repair
CC proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16
CC (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is
CC initiated by RNF168 that mediates monoubiquitination at these 2 sites,
CC and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin;
CC RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro.
CC H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination
CC (H2AK13Ub and H2AK15Ub) are distinct events (By similarity).
CC {ECO:0000250|UniProtKB:P16104}.
CC -!- PTM: Acetylation at Lys-6 (H2AXK5ac) by KAT5 component of the NuA4
CC histone acetyltransferase complex promotes NBN/NBS1 assembly at the
CC sites of DNA damage (By similarity). Acetylation at Lys-37 increases in
CC S and G2 phases (PubMed:20488183, PubMed:7217105). This modification
CC has been proposed to be important for DNA double-strand break repair
CC (PubMed:20488183). {ECO:0000250|UniProtKB:P16104,
CC ECO:0000269|PubMed:20488183, ECO:0000269|PubMed:7217105}.
CC -!- MISCELLANEOUS: Haploinsufficient for the suppression of genomic
CC instability. This phenotype is further exacerbated in the absence of
CC TP53.
CC -!- SIMILARITY: Belongs to the histone H2A family. {ECO:0000305}.
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DR EMBL; X58069; CAA41099.1; -; mRNA.
DR EMBL; Z35401; CAA84585.1; -; Genomic_DNA.
DR EMBL; BC005468; AAH05468.1; -; mRNA.
DR EMBL; BC010336; AAH10336.1; -; mRNA.
DR CCDS; CCDS23105.1; -.
DR PIR; I48406; I48406.
DR RefSeq; NP_034566.1; NM_010436.2.
DR AlphaFoldDB; P27661; -.
DR SMR; P27661; -.
DR BioGRID; 200313; 21.
DR IntAct; P27661; 12.
DR MINT; P27661; -.
DR STRING; 10090.ENSMUSP00000051432; -.
DR iPTMnet; P27661; -.
DR PhosphoSitePlus; P27661; -.
DR SwissPalm; P27661; -.
DR EPD; P27661; -.
DR jPOST; P27661; -.
DR MaxQB; P27661; -.
DR PaxDb; P27661; -.
DR PeptideAtlas; P27661; -.
DR PRIDE; P27661; -.
DR ProteomicsDB; 271118; -.
DR TopDownProteomics; P27661; -.
DR Antibodypedia; 3220; 1601 antibodies from 47 providers.
DR DNASU; 15270; -.
DR Ensembl; ENSMUST00000052686; ENSMUSP00000051432; ENSMUSG00000049932.
DR GeneID; 15270; -.
DR KEGG; mmu:15270; -.
DR UCSC; uc009pcy.1; mouse.
DR CTD; 3014; -.
DR MGI; MGI:102688; H2ax.
DR VEuPathDB; HostDB:ENSMUSG00000049932; -.
DR eggNOG; KOG1756; Eukaryota.
DR GeneTree; ENSGT01020000230360; -.
DR HOGENOM; CLU_062828_3_1_1; -.
DR InParanoid; P27661; -.
DR OMA; ATHSHEK; -.
DR OrthoDB; 1504122at2759; -.
DR PhylomeDB; P27661; -.
DR TreeFam; TF300137; -.
DR Reactome; R-MMU-110330; Recognition and association of DNA glycosylase with site containing an affected purine.
DR Reactome; R-MMU-110331; Cleavage of the damaged purine.
DR Reactome; R-MMU-212300; PRC2 methylates histones and DNA.
DR Reactome; R-MMU-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-MMU-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-MMU-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-MMU-427359; SIRT1 negatively regulates rRNA expression.
DR Reactome; R-MMU-427413; NoRC negatively regulates rRNA expression.
DR Reactome; R-MMU-5250924; B-WICH complex positively regulates rRNA expression.
DR Reactome; R-MMU-5578749; Transcriptional regulation by small RNAs.
DR Reactome; R-MMU-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-606279; Deposition of new CENPA-containing nucleosomes at the centromere.
DR Reactome; R-MMU-68616; Assembly of the ORC complex at the origin of replication.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR Reactome; R-MMU-73728; RNA Polymerase I Promoter Opening.
DR Reactome; R-MMU-73772; RNA Polymerase I Promoter Escape.
DR Reactome; R-MMU-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-MMU-9018519; Estrogen-dependent gene expression.
DR Reactome; R-MMU-9670095; Inhibition of DNA recombination at telomere.
DR BioGRID-ORCS; 15270; 12 hits in 110 CRISPR screens.
DR ChiTaRS; H2afx; mouse.
DR PRO; PR:P27661; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P27661; protein.
DR Bgee; ENSMUSG00000049932; Expressed in medial ganglionic eminence and 258 other tissues.
DR Genevisible; P27661; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; IDA:MGI.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:MGI.
DR GO; GO:0001673; C:male germ cell nucleus; IDA:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000786; C:nucleosome; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005657; C:replication fork; IDA:MGI.
DR GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:MGI.
DR GO; GO:0001741; C:XY body; IDA:MGI.
DR GO; GO:0003684; F:damaged DNA binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042393; F:histone binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0030527; F:structural constituent of chromatin; IEA:InterPro.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0071480; P:cellular response to gamma radiation; ISO:MGI.
DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0006281; P:DNA repair; IDA:MGI.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:MGI.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR CDD; cd00074; H2A; 1.
DR Gene3D; 1.10.20.10; -; 1.
DR InterPro; IPR009072; Histone-fold.
DR InterPro; IPR002119; Histone_H2A.
DR InterPro; IPR007125; Histone_H2A/H2B/H3.
DR InterPro; IPR032454; Histone_H2A_C.
DR InterPro; IPR032458; Histone_H2A_CS.
DR PANTHER; PTHR23430; PTHR23430; 1.
DR Pfam; PF00125; Histone; 1.
DR Pfam; PF16211; Histone_H2A_C; 1.
DR PRINTS; PR00620; HISTONEH2A.
DR SMART; SM00414; H2A; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR PROSITE; PS00046; HISTONE_H2A; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell cycle; Chromosome; DNA damage; DNA recombination;
KW DNA repair; DNA-binding; Isopeptide bond; Meiosis; Nucleosome core;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7217105"
FT CHAIN 2..143
FT /note="Histone H2AX"
FT /id="PRO_0000055243"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 121..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 140..141
FT /note="[ST]-Q motif"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|PubMed:7217105"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:7217105"
FT MOD_RES 6
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 10
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 10
FT /note="N6-lactoyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0C0S5"
FT MOD_RES 37
FT /note="N6-acetyllysine; by CREBBP and EP300"
FT /evidence="ECO:0000269|PubMed:20488183"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 140
FT /note="Phosphoserine; by ATM, ATR and PRKDC"
FT /evidence="ECO:0000269|PubMed:11242108,
FT ECO:0000269|PubMed:11571274, ECO:0000269|PubMed:11740565,
FT ECO:0000269|PubMed:12447390, ECO:0000269|PubMed:12660252,
FT ECO:0000269|PubMed:14530383, ECO:0000269|PubMed:15059890,
FT ECO:0000269|PubMed:15580272, ECO:0000269|PubMed:9488723,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 143
FT /note="Phosphotyrosine; by WSTF"
FT /evidence="ECO:0000269|PubMed:19092802"
FT CROSSLNK 14
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P16104"
FT CROSSLNK 16
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P16104"
FT CROSSLNK 120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:7407044"
FT CROSSLNK 128
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P16104"
FT CROSSLNK 135
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P16104"
FT MUTAGEN 6
FT /note="K->A: No effect on radiosensitivity; when associated
FT with A-10, A-14 and A-16."
FT /evidence="ECO:0000269|PubMed:20488183"
FT MUTAGEN 10
FT /note="K->A: No effect on radiosensitivity; when associated
FT with A-6, A-14 and A-16."
FT /evidence="ECO:0000269|PubMed:20488183"
FT MUTAGEN 14
FT /note="K->A: No effect on radiosensitivity; when associated
FT with A-6, A-10 and A-16."
FT /evidence="ECO:0000269|PubMed:20488183"
FT MUTAGEN 16
FT /note="K->A: No effect on radiosensitivity; when associated
FT with A-6, A-10 and A-14."
FT /evidence="ECO:0000269|PubMed:20488183"
FT MUTAGEN 37
FT /note="K->A: Increased radiosensitivity. No effect on
FT phosphorylation after DNA damage. No effect on Ser-140
FT phosphorylation, nor on TP53BP1 recruitment to DNA double-
FT strand breaks."
FT /evidence="ECO:0000269|PubMed:20488183"
FT MUTAGEN 37
FT /note="K->R: No effect on phosphorylation after DNA damage,
FT but increased radiosensitivity. Further increase in
FT radiosensitivity; when associated with A-140."
FT /evidence="ECO:0000269|PubMed:20488183"
FT MUTAGEN 119..120
FT /note="KK->AA: Complete loss of ubiquitination and
FT increased radiosensitivity."
FT /evidence="ECO:0000269|PubMed:20488183"
FT MUTAGEN 137
FT /note="S->A: Increased genomic instability and
FT radiosensitivity; when associated with A-140."
FT /evidence="ECO:0000269|PubMed:12914701"
FT MUTAGEN 140
FT /note="S->A: Increased genomic instability and
FT radiosensitivity; when associated with A-137. Reduced
FT homologous recombination. No effect on Lys-40 acetylation.
FT Further increase in radiosensitivity; when associated with
FT R-37."
FT /evidence="ECO:0000269|PubMed:12914701,
FT ECO:0000269|PubMed:15610743, ECO:0000269|PubMed:20488183"
SQ SEQUENCE 143 AA; 15143 MW; A3683760C13CC2B9 CRC64;
MSGRGKTGGK ARAKAKSRSS RAGLQFPVGR VHRLLRKGHY AERVGAGAPV YLAAVLEYLT
AEILELAGNA ARDNKKTRII PRHLQLAIRN DEELNKLLGG VTIAQGGVLP NIQAVLLPKK
SSATVGPKAP AVGKKASQAS QEY
